APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma

NCT02706353 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2015-0654NCI-2016-00675
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

You are being asked to take part in this study because you have metastatic (cancer that has spread) melanoma. The goal of Part 1 of this clinical research study is to find the highest tolerable dose of APX005M that can be given with pembrolizumab that can be given to patients with metastatic melanoma. The goal of Part 2 of this study is to learn if the combination can help to control metastatic melanoma. The safety of this drug combination will also be studied. This is an investigational study. APX005M is not FDA approved or commercially available. It is currently being used for research purposes only. Pembrolizumab is FDA approved and commercially available for the treatment of metastatic melanoma. The combination of these drugs to treat metastatic melanoma is investigational. The study doctor can explain how the study drug is designed to work. Up to 41 participants will be treated in this study. All will take part at MD Anderson.

Conditions

Melanoma

Keywords

Melanoma; Metastatic Melanoma; Intratumoral APX005M; Pembrolizumab; Keytruda; MK-3475; SCH-900475

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability

  To assess safety and tolerability of intratumoral APX005M given with systemic pembrolizumab and identify of the maximum tolerated dose/recommended phase 2 dose (MTD/PR2D) of the combination therapy in patients with metastatic melanoma.

  Baseline to 2 years

• Overall Response Rate (ORR)

  To assess best overall response after ibtratumoral injection of APX005M in combination with systemic pembrolizumab

  Baseline to 2 years

Secondary Outcomes (3)

• Evaluation of Intratumoral CD8⁺ T Cells

  Baseline to week 6

• Overall Safety and Tolerability

  Baseline to 2 years

• Anti-tumor Immune Responses and Clinical Efficacy

  Baseline to 2 years

Study Arms (1)

APX005M + Pembrolizumab

EXPERIMENTAL

Dose Escalation Phase: Starting dose level of APX005M is 0.1 mg injected directly into 1-3 tumors every 3 weeks (Weeks 0, 3, 6, and 9) for up to 4 doses. Tumor site chosen based on volume to be injected. All participants receive Pembrolizumab at 2 mg/kg by vein 1 time every 3 weeks (Weeks 0, 3, 6, 9, and 12). First dose of Pembrolizumab given 1-2 days before or after first dose of APX005M. Dose Expansion Phase: Starting dose level of APX005M is maximum tolerated dose from Dose Escalation Phase. Participants receive same dosage of Pembrolizumab as in Dose Escalation Phase.

Drug: APX005M; Drug: Pembrolizumab

Interventions

APX005M DRUG

Dose Escalation Phase Starting Dose Level of APX005M: 0.1 mg injected directly into 1-3 tumors every 3 weeks (Weeks 0, 3, 6, and 9) for up to 4 doses. Dose Expansion Phase Starting Dose Level of APX005M: Maximum tolerated dose from Dose Escalation Phase.

APX005M + Pembrolizumab

Pembrolizumab DRUG

Dose Escalation and Expansion Phase Dose of Pembrolizumab: 2 mg/kg by vein 1 time every 3 weeks (Weeks 0, 3, 6, 9, and 12). First dose of Pembrolizumab given 1-2 days before or after first dose of APX005M.

Also known as: Keytruda, MK-3475, SCH-900475

APX005M + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Histologically or cytologically confirmed malignant melanoma from skin, or mucosal melanoma (i.e. ocular melanoma subjects are not eligible)
• Measurable, unresectable stage III (in transit lesions) or stage IVA, IVB, IVC disease
• At least two injectable lesions (amenable for direct injection or through the use of image guidance such ultrasound \[US\], CT or MRI) defined as any injectable cutaneous, subcutaneous, nodal, or visceral melanoma lesion ≥ 10 mm in longest diameter
• Age ≥ 18 years
• ECOG performance status 0 or 1
• Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
• Platelet count greater than or equal to 100,000/mm\^3
• WBC \>3000/mm\^3
• ANC \> 1500/mm\^3
• Hemoglobin \>9 g/dL
• Serum ALT and AST \<3 the upper limit of normal (ULN); \<5 ULN if there is liver involvement secondary to the tumor
• Serum creatinine \< 2.0 mg/dl
• Seronegative for HIV antibody
• Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP). A WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not had menses at any time in the preceding 12 consecutive months). Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study and for 4 months after the last dose of APX005M or Pembrolizumab such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control.

You may not qualify if:

• Patients who have previously received pembrolizumab or PD-/L1 blockade therapy. Adjuvant IFN-a, is allowed if last dose was received at least 6 months of starting study treatment.
• Active autoimmune disease requiring disease-modifying therapy.
• Concurrent systemic steroid therapy higher than physiologic dose (\>7.5 mg/day of prednisone or equivalent).
• Any form of active primary or secondary immunodeficiency.
• History of hematologic malignancy.
• Active coagulopathy.
• History of New York Heart Association class 3-4 congestive heart failure or history myocardial infarction within 6 months of starting study treatment.
• History of arterial thrombosis within 3 months of starting study treatment.
• Patients with known symptomatic brain metastases requiring systematic corticosteroids. Patients with previous diagnosed brain metastases are eligible if they have completed their treatment and have recovered from acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for their metastases for at least 2 weeks and are neurologically stable. Mild neurological deficits are allowed, if they do not interfere with the ability to judge the safety profile of APX005M.
• Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
• Subjects who have received prior immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1), anti-CD40.
• Subjects that have received experimental vaccines or other immune therapies should be discussed with the Principal Investigator to confirm eligibility.
• Active known clinically serious infections (\> Grade 2 NCI-CTCAE version 4.03).
• Prior systemic therapy, radiation therapy, or surgery within the 28 days of starting study treatment. Palliative radiotherapy to a limited field or palliative cryoablation is allowed after consultation with the Principal Investigator, at any time during the study participation including screening.
• Women of child-bearing potential (WOCBP), women who are pregnant, or women who are nursing.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Apexigen America, Inc.: collaborator
• Pyxis Oncology: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

sotigalimab; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Adi Diab, MD
• Organization: M.D. Anderson Cancer Center

MDADiab@mdanderson.org

713-792-2921

Study Officials

• Adi Diab, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 11, 2016
• Study Start: June 2, 2017
• Primary Completion: March 10, 2025
• Study Completion: March 10, 2025
• Last Updated: November 21, 2025
• Results First Posted: November 21, 2025

Record last verified: 2025-11

Locations

US (1)